1. Field of the Invention
This invention concerns novel tetrazole, acylhydroxylamine, hydroxymethylketone and amide derivatives of unsaturated fatty acids and, where applicable, their pharmaceutically acceptable salts, their use in the prevention and treatment of inflammatory processes, pain and allergic reactions, and pharmaceutical compositions containing these compounds and methods of their preparation.
Arachidonic acid is the biological precursor of such pro-inflammatory agents as prostaglandins and leucotrienes, or the platelet aggregation inducers thromboxanes. Compounds of this invention show selective inhibitory activity on the enzymes involved in the metabolic synthetic pathways of prostaglandins, leucotrienes or thromboxanes. These compounds will be beneficial in the prevention or treatment of inflammatory and painful disorders, such as rheumatoid arthritis, or in the prevention or treatment of disorders of allergic origin, such as bronchospasm in asthma.
2. Related Disclosures
Those compounds closest in structure to those of the present invention are 2-descarboxy-2-(tetrazol-5-yl) prostaglandins disclosed in Dutch Pat. No. NL-7,211,860Q; N-(hydroxyalkyl) aliphatic amides disclosed in Belgium Pat. BE No. 785,292Q; Vitamin F compounds disclosed in French Pat. No. 2,264,522; long-chain fatty acid amides disclosed in French Pat. No. 2,140,369Q; unsaturated fatty acid amides disclosed in British Pat. No. 1,074,693 and 16-24 carbon unsaturated fatty acid amides disclosed in Dutch Pat. Neth. No. 6,604,058; quarternary ammonium hydroxamates are described in U.S. Pat. No. 3,427,316, and N-substituted fatty acid amides as cholesterol lowering agents are described in U.S. Pat. No. 3,995,059.
J.Med.Chem., 12:1184(1975) describes analogs of lysophosphatidylethanolamine which inhibit renin activity. Eicosatetrayn-5,8,11,14-oic acid and its salts and esters are described in Belgium Pat. No. 711,448.